title: Noradrenergic-glucocorticoid modulation of emotional memory encoding in the human hippocampus.
abstract: BACKGROUND
  Current rodent models emphasize the joint action of the stress mediators noradrenaline (NE) and cortisol (CORT) in conferring a memory advantage of emotional over neutral stimuli.
  
  
  METHODS
  Using a pharmacological strategy of tackling this stress-related mechanism to enhance human episodic (autobiographical) memory, we measured amygdala-hippocampal responses during encoding of emotional and neutral stimuli with functional magnetic resonance imaging in 51 healthy subjects under four pharmacological conditions in a double-blind parallel group design: (i) placebo; (ii) the NE-reuptake inhibitor reboxetine (4 mg); (iii) hydrocortisone (synthetic CORT) (30 mg); or (iv) both agents in combination.
  
  
  RESULTS
  Differential drug effects were found in the left hippocampus, whereas hydrocortisone alone selectively decreased hippocampal responses to emotional relative to neutral stimuli, reboxetine potentiated hippocampal responses to these stimuli. Importantly, the inhibitory influence of hydrocortisone was reversed by co-administration of reboxetine.
  
  
  CONCLUSIONS
  Our results imply that stress levels of CORT alone attenuate hippocampal responses to emotional stimuli, an effect possibly related to a regulatory negative feedback loop. However, when simultaneously elevated to stress levels, NE and CORT act together to synergistically enhance hippocampal activity during encoding of emotional stimuli, a mechanism that may turn maladaptive under circumstances of traumatic stress.
authors.affiliation: Department of Psychiatry, University of Bonn, Bonn, Germany. juraj.kukolja@uk-koeln.de
authors.forename: J
authors.initials: J
authors.lastname: Kukolja
authors.forename: D
authors.initials: D
authors.lastname: Klingmüller
authors.forename: W
authors.initials: W
authors.lastname: Maier
authors.forename: G R
authors.initials: GR
authors.lastname: Fink
authors.forename: R
authors.initials: R
authors.lastname: Hurlemann
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000679:Amygdala / Q000187:drug effects; D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005938:Glucocorticoids; D006624:Hippocampus / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology*; D010919:Placebos; D000077593:Reboxetine; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D009025:Morpholines; D010919:Placebos; D000077593:Reboxetine; D006854:Hydrocortisone